CA2671838A1 - 4-imidazolines as taar's ligands - Google Patents
4-imidazolines as taar's ligands Download PDFInfo
- Publication number
- CA2671838A1 CA2671838A1 CA002671838A CA2671838A CA2671838A1 CA 2671838 A1 CA2671838 A1 CA 2671838A1 CA 002671838 A CA002671838 A CA 002671838A CA 2671838 A CA2671838 A CA 2671838A CA 2671838 A1 CA2671838 A1 CA 2671838A1
- Authority
- CA
- Canada
- Prior art keywords
- imidazole
- formula
- compound
- phenyl
- disorders
- Prior art date
- Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)
- Abandoned
Links
- 239000003446 ligand Substances 0.000 title description 5
- LWTIGYSPAXKMDG-UHFFFAOYSA-N 2,3-dihydro-1h-imidazole Chemical class C1NC=CN1 LWTIGYSPAXKMDG-UHFFFAOYSA-N 0.000 title 1
- 150000001875 compounds Chemical class 0.000 claims abstract description 119
- -1 hydroxy, amino Chemical group 0.000 claims abstract description 52
- 125000000217 alkyl group Chemical group 0.000 claims abstract description 25
- 239000002253 acid Substances 0.000 claims abstract description 20
- 150000003839 salts Chemical class 0.000 claims abstract description 20
- 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 claims abstract description 18
- 208000035475 disorder Diseases 0.000 claims abstract description 15
- 229910052736 halogen Inorganic materials 0.000 claims abstract description 13
- 150000002367 halogens Chemical group 0.000 claims abstract description 13
- 238000011282 treatment Methods 0.000 claims abstract description 12
- 208000018737 Parkinson disease Diseases 0.000 claims abstract description 11
- 239000001257 hydrogen Substances 0.000 claims abstract description 11
- 229910052739 hydrogen Inorganic materials 0.000 claims abstract description 11
- 208000006096 Attention Deficit Disorder with Hyperactivity Diseases 0.000 claims abstract description 10
- 125000003545 alkoxy group Chemical group 0.000 claims abstract description 9
- 208000019901 Anxiety disease Diseases 0.000 claims abstract description 8
- 208000030814 Eating disease Diseases 0.000 claims abstract description 7
- 208000019454 Feeding and Eating disease Diseases 0.000 claims abstract description 7
- 208000019695 Migraine disease Diseases 0.000 claims abstract description 7
- 235000014632 disordered eating Nutrition 0.000 claims abstract description 7
- 206010027599 migraine Diseases 0.000 claims abstract description 7
- 201000000980 schizophrenia Diseases 0.000 claims abstract description 7
- 201000009032 substance abuse Diseases 0.000 claims abstract description 7
- 231100000736 substance abuse Toxicity 0.000 claims abstract description 7
- 208000011117 substance-related disease Diseases 0.000 claims abstract description 7
- 208000020401 Depressive disease Diseases 0.000 claims abstract description 6
- 125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 claims abstract description 6
- 208000024827 Alzheimer disease Diseases 0.000 claims abstract description 5
- 208000020925 Bipolar disease Diseases 0.000 claims abstract description 5
- 208000002249 Diabetes Complications Diseases 0.000 claims abstract description 5
- 206010012655 Diabetic complications Diseases 0.000 claims abstract description 5
- 230000036760 body temperature Effects 0.000 claims abstract description 5
- 206010012601 diabetes mellitus Diseases 0.000 claims abstract description 5
- 206010015037 epilepsy Diseases 0.000 claims abstract description 5
- 230000013632 homeostatic process Effects 0.000 claims abstract description 5
- 230000007257 malfunction Effects 0.000 claims abstract description 5
- 125000002924 primary amino group Chemical group [H]N([H])* 0.000 claims abstract description 5
- 125000004435 hydrogen atom Chemical group [H]* 0.000 claims abstract description 4
- 125000000499 benzofuranyl group Chemical group O1C(=CC2=C1C=CC=C2)* 0.000 claims abstract description 3
- 125000001797 benzyl group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C([H])([H])* 0.000 claims abstract description 3
- 125000000051 benzyloxy group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C([H])([H])O* 0.000 claims abstract description 3
- 125000002757 morpholinyl group Chemical group 0.000 claims abstract description 3
- 125000001424 substituent group Chemical group 0.000 claims abstract description 3
- RAXXELZNTBOGNW-UHFFFAOYSA-N imidazole Substances C1=CNC=N1 RAXXELZNTBOGNW-UHFFFAOYSA-N 0.000 claims description 31
- WEVYAHXRMPXWCK-UHFFFAOYSA-N Acetonitrile Chemical compound CC#N WEVYAHXRMPXWCK-UHFFFAOYSA-N 0.000 claims description 30
- 238000000034 method Methods 0.000 claims description 23
- 239000003814 drug Substances 0.000 claims description 8
- 230000008569 process Effects 0.000 claims description 7
- 208000036864 Attention deficit/hyperactivity disease Diseases 0.000 claims description 6
- 208000015802 attention deficit-hyperactivity disease Diseases 0.000 claims description 6
- XAXVKFPHORMPIN-UHFFFAOYSA-N 5-(2-phenylbutyl)-1h-imidazole Chemical compound C=1C=CC=CC=1C(CC)CC1=CNC=N1 XAXVKFPHORMPIN-UHFFFAOYSA-N 0.000 claims description 5
- YWVYIQHMRCZWSF-UHFFFAOYSA-N 5-methyl-4-(phenylsulfanylmethyl)-1h-imidazole Chemical compound N1C=NC(CSC=2C=CC=CC=2)=C1C YWVYIQHMRCZWSF-UHFFFAOYSA-N 0.000 claims description 5
- RIXSQSPZGHVLRC-UHFFFAOYSA-N 5-(2-phenylpropyl)-1h-imidazole Chemical compound C=1C=CC=CC=1C(C)CC1=CNC=N1 RIXSQSPZGHVLRC-UHFFFAOYSA-N 0.000 claims description 4
- INDQMNBWYUOPOD-UHFFFAOYSA-N 5-[(2,3-dichlorophenoxy)methyl]-1h-imidazole Chemical compound ClC1=CC=CC(OCC=2N=CNC=2)=C1Cl INDQMNBWYUOPOD-UHFFFAOYSA-N 0.000 claims description 4
- GLVMMYLDOKCSNY-UHFFFAOYSA-N 5-[(2-fluorophenoxy)methyl]-1h-imidazole Chemical compound FC1=CC=CC=C1OCC1=CNC=N1 GLVMMYLDOKCSNY-UHFFFAOYSA-N 0.000 claims description 4
- 238000002360 preparation method Methods 0.000 claims description 4
- 230000036506 anxiety Effects 0.000 claims description 3
- 125000002887 hydroxy group Chemical group [H]O* 0.000 claims description 3
- LPNIQLNETDLCSC-UHFFFAOYSA-N 4-[(4-chlorophenyl)sulfanylmethyl]-5-methyl-1H-imidazole 5-(naphthalen-2-ylsulfanylmethyl)-1H-imidazole Chemical compound C1=C(C=CC2=CC=CC=C12)SCC=1N=CNC1.ClC1=CC=C(C=C1)SCC=1N=CNC1C LPNIQLNETDLCSC-UHFFFAOYSA-N 0.000 claims description 2
- 101100109871 Neurospora crassa (strain ATCC 24698 / 74-OR23-1A / CBS 708.71 / DSM 1257 / FGSC 987) aro-8 gene Proteins 0.000 claims description 2
- 230000002152 alkylating effect Effects 0.000 claims description 2
- 230000001590 oxidative effect Effects 0.000 claims description 2
- UKBSXGYFMFJQRN-UHFFFAOYSA-N 5-[(3-chlorophenoxy)methyl]-1h-imidazole;5-[(2-methylphenoxy)methyl]-1h-imidazole Chemical compound CC1=CC=CC=C1OCC1=CN=CN1.ClC1=CC=CC(OCC=2NC=NC=2)=C1 UKBSXGYFMFJQRN-UHFFFAOYSA-N 0.000 claims 1
- 108050002178 Trace amine associated receptor Proteins 0.000 abstract description 16
- 102000011829 Trace amine associated receptor Human genes 0.000 abstract description 14
- 101000890887 Homo sapiens Trace amine-associated receptor 1 Proteins 0.000 abstract description 8
- 102100040114 Trace amine-associated receptor 1 Human genes 0.000 abstract description 8
- 208000028017 Psychotic disease Diseases 0.000 abstract description 6
- 208000030159 metabolic disease Diseases 0.000 abstract description 4
- 208000024172 Cardiovascular disease Diseases 0.000 abstract description 3
- 208000017164 Chronobiology disease Diseases 0.000 abstract description 3
- 208000032928 Dyslipidaemia Diseases 0.000 abstract description 3
- 206010020772 Hypertension Diseases 0.000 abstract description 3
- 208000017170 Lipid metabolism disease Diseases 0.000 abstract description 3
- 208000012902 Nervous system disease Diseases 0.000 abstract description 3
- 208000025966 Neurological disease Diseases 0.000 abstract description 3
- 208000008589 Obesity Diseases 0.000 abstract description 3
- 230000027288 circadian rhythm Effects 0.000 abstract description 3
- 238000005265 energy consumption Methods 0.000 abstract description 3
- 208000015122 neurodegenerative disease Diseases 0.000 abstract description 3
- 235000020824 obesity Nutrition 0.000 abstract description 3
- 230000007958 sleep Effects 0.000 abstract description 3
- OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 111
- WYURNTSHIVDZCO-UHFFFAOYSA-N Tetrahydrofuran Chemical compound C1CCOC1 WYURNTSHIVDZCO-UHFFFAOYSA-N 0.000 description 58
- XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 description 57
- 239000007787 solid Substances 0.000 description 51
- ADCUCAMWCWNHJA-UHFFFAOYSA-N 4-(chloromethyl)-1-tritylimidazole Chemical compound C1=NC(CCl)=CN1C(C=1C=CC=CC=1)(C=1C=CC=CC=1)C1=CC=CC=C1 ADCUCAMWCWNHJA-UHFFFAOYSA-N 0.000 description 47
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 44
- ZMXDDKWLCZADIW-UHFFFAOYSA-N N,N-Dimethylformamide Chemical compound CN(C)C=O ZMXDDKWLCZADIW-UHFFFAOYSA-N 0.000 description 44
- 239000000203 mixture Substances 0.000 description 38
- 239000000243 solution Substances 0.000 description 37
- YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 description 33
- HEMHJVSKTPXQMS-UHFFFAOYSA-M Sodium hydroxide Chemical compound [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 description 29
- 235000019439 ethyl acetate Nutrition 0.000 description 26
- 239000002904 solvent Substances 0.000 description 26
- FNSMDCRPGWSMDB-UHFFFAOYSA-N 4-(diethoxyphosphorylmethyl)-1-tritylimidazole Chemical compound C1=NC(CP(=O)(OCC)OCC)=CN1C(C=1C=CC=CC=1)(C=1C=CC=CC=1)C1=CC=CC=C1 FNSMDCRPGWSMDB-UHFFFAOYSA-N 0.000 description 22
- RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 description 22
- ZMANZCXQSJIPKH-UHFFFAOYSA-N Triethylamine Chemical compound CCN(CC)CC ZMANZCXQSJIPKH-UHFFFAOYSA-N 0.000 description 21
- CSNNHWWHGAXBCP-UHFFFAOYSA-L Magnesium sulfate Chemical compound [Mg+2].[O-][S+2]([O-])([O-])[O-] CSNNHWWHGAXBCP-UHFFFAOYSA-L 0.000 description 18
- YXFVVABEGXRONW-UHFFFAOYSA-N Toluene Chemical compound CC1=CC=CC=C1 YXFVVABEGXRONW-UHFFFAOYSA-N 0.000 description 18
- QTBSBXVTEAMEQO-UHFFFAOYSA-N Acetic acid Chemical compound CC(O)=O QTBSBXVTEAMEQO-UHFFFAOYSA-N 0.000 description 17
- VYPSYNLAJGMNEJ-UHFFFAOYSA-N Silicium dioxide Chemical compound O=[Si]=O VYPSYNLAJGMNEJ-UHFFFAOYSA-N 0.000 description 17
- 239000012300 argon atmosphere Substances 0.000 description 17
- 239000000741 silica gel Substances 0.000 description 17
- 229910002027 silica gel Inorganic materials 0.000 description 17
- XDTMQSROBMDMFD-UHFFFAOYSA-N Cyclohexane Chemical compound C1CCCCC1 XDTMQSROBMDMFD-UHFFFAOYSA-N 0.000 description 16
- KWYUFKZDYYNOTN-UHFFFAOYSA-M Potassium hydroxide Chemical compound [OH-].[K+] KWYUFKZDYYNOTN-UHFFFAOYSA-M 0.000 description 15
- 239000002585 base Substances 0.000 description 15
- 238000004440 column chromatography Methods 0.000 description 15
- 239000012043 crude product Substances 0.000 description 15
- 229910052943 magnesium sulfate Inorganic materials 0.000 description 13
- 238000010992 reflux Methods 0.000 description 13
- 125000002221 trityl group Chemical group [H]C1=C([H])C([H])=C([H])C([H])=C1C([*])(C1=C(C(=C(C(=C1[H])[H])[H])[H])[H])C1=C([H])C([H])=C([H])C([H])=C1[H] 0.000 description 13
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 12
- 239000003921 oil Substances 0.000 description 11
- 235000019198 oils Nutrition 0.000 description 11
- 125000006239 protecting group Chemical group 0.000 description 11
- IAZDPXIOMUYVGZ-UHFFFAOYSA-N Dimethylsulphoxide Chemical compound CS(C)=O IAZDPXIOMUYVGZ-UHFFFAOYSA-N 0.000 description 10
- VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 description 10
- 230000015572 biosynthetic process Effects 0.000 description 10
- 239000000725 suspension Substances 0.000 description 10
- CSCPPACGZOOCGX-UHFFFAOYSA-N Acetone Chemical compound CC(C)=O CSCPPACGZOOCGX-UHFFFAOYSA-N 0.000 description 9
- 230000029936 alkylation Effects 0.000 description 9
- 238000005804 alkylation reaction Methods 0.000 description 9
- 150000001412 amines Chemical class 0.000 description 9
- 235000019341 magnesium sulphate Nutrition 0.000 description 9
- 239000011541 reaction mixture Substances 0.000 description 9
- QAOWNCQODCNURD-UHFFFAOYSA-N Sulfuric acid Chemical compound OS(O)(=O)=O QAOWNCQODCNURD-UHFFFAOYSA-N 0.000 description 8
- 239000003054 catalyst Substances 0.000 description 8
- 238000004519 manufacturing process Methods 0.000 description 8
- LPNYRYFBWFDTMA-UHFFFAOYSA-N potassium tert-butoxide Chemical compound [K+].CC(C)(C)[O-] LPNYRYFBWFDTMA-UHFFFAOYSA-N 0.000 description 8
- 238000003786 synthesis reaction Methods 0.000 description 8
- KDLHZDBZIXYQEI-UHFFFAOYSA-N Palladium on carbon Substances [Pd] KDLHZDBZIXYQEI-UHFFFAOYSA-N 0.000 description 7
- NBIIXXVUZAFLBC-UHFFFAOYSA-N Phosphoric acid Chemical compound OP(O)(O)=O NBIIXXVUZAFLBC-UHFFFAOYSA-N 0.000 description 7
- UIIMBOGNXHQVGW-UHFFFAOYSA-M Sodium bicarbonate Chemical compound [Na+].OC([O-])=O UIIMBOGNXHQVGW-UHFFFAOYSA-M 0.000 description 7
- 239000000969 carrier Substances 0.000 description 7
- 238000006243 chemical reaction Methods 0.000 description 7
- 229910000027 potassium carbonate Inorganic materials 0.000 description 7
- HPALAKNZSZLMCH-UHFFFAOYSA-M sodium;chloride;hydrate Chemical compound O.[Na+].[Cl-] HPALAKNZSZLMCH-UHFFFAOYSA-M 0.000 description 7
- 238000003756 stirring Methods 0.000 description 7
- UHOVQNZJYSORNB-UHFFFAOYSA-N Benzene Chemical compound C1=CC=CC=C1 UHOVQNZJYSORNB-UHFFFAOYSA-N 0.000 description 6
- UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 description 6
- CDBYLPFSWZWCQE-UHFFFAOYSA-L Sodium Carbonate Chemical compound [Na+].[Na+].[O-]C([O-])=O CDBYLPFSWZWCQE-UHFFFAOYSA-L 0.000 description 6
- WQDUMFSSJAZKTM-UHFFFAOYSA-N Sodium methoxide Chemical compound [Na+].[O-]C WQDUMFSSJAZKTM-UHFFFAOYSA-N 0.000 description 6
- 239000012267 brine Substances 0.000 description 6
- 239000002775 capsule Substances 0.000 description 6
- KRKNYBCHXYNGOX-UHFFFAOYSA-N citric acid Chemical compound OC(=O)CC(O)(C(O)=O)CC(O)=O KRKNYBCHXYNGOX-UHFFFAOYSA-N 0.000 description 6
- 238000003776 cleavage reaction Methods 0.000 description 6
- 229960004132 diethyl ether Drugs 0.000 description 6
- MZRVEZGGRBJDDB-UHFFFAOYSA-N n-Butyllithium Substances [Li]CCCC MZRVEZGGRBJDDB-UHFFFAOYSA-N 0.000 description 6
- NLKNQRATVPKPDG-UHFFFAOYSA-M potassium iodide Chemical compound [K+].[I-] NLKNQRATVPKPDG-UHFFFAOYSA-M 0.000 description 6
- 239000000047 product Substances 0.000 description 6
- 230000007017 scission Effects 0.000 description 6
- RYHBNJHYFVUHQT-UHFFFAOYSA-N 1,4-Dioxane Chemical compound C1COCCO1 RYHBNJHYFVUHQT-UHFFFAOYSA-N 0.000 description 5
- TZBRCDMGXKRTCN-UHFFFAOYSA-N 2-[tert-butyl(dimethyl)silyl]-n,n-dimethylimidazole-1-sulfonamide Chemical compound CN(C)S(=O)(=O)N1C=CN=C1[Si](C)(C)C(C)(C)C TZBRCDMGXKRTCN-UHFFFAOYSA-N 0.000 description 5
- 150000001336 alkenes Chemical class 0.000 description 5
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- 235000011007 phosphoric acid Nutrition 0.000 description 5
- 238000000746 purification Methods 0.000 description 5
- 150000003462 sulfoxides Chemical class 0.000 description 5
- CGWCKWISXYESMC-UHFFFAOYSA-N 5-(2,2-diphenylethyl)-1h-imidazole Chemical compound C=1N=CNC=1CC(C=1C=CC=CC=1)C1=CC=CC=C1 CGWCKWISXYESMC-UHFFFAOYSA-N 0.000 description 4
- UFVVSLRERVDQAI-UHFFFAOYSA-N 5-(2-phenylethyl)-1h-imidazole Chemical compound C=1NC=NC=1CCC1=CC=CC=C1 UFVVSLRERVDQAI-UHFFFAOYSA-N 0.000 description 4
- CPELXLSAUQHCOX-UHFFFAOYSA-M Bromide Chemical compound [Br-] CPELXLSAUQHCOX-UHFFFAOYSA-M 0.000 description 4
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- 229910004373 HOAc Inorganic materials 0.000 description 4
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- AFVFQIVMOAPDHO-UHFFFAOYSA-N Methanesulfonic acid Chemical compound CS(O)(=O)=O AFVFQIVMOAPDHO-UHFFFAOYSA-N 0.000 description 4
- JGFZNNIVVJXRND-UHFFFAOYSA-N N,N-Diisopropylethylamine (DIPEA) Chemical compound CCN(C(C)C)C(C)C JGFZNNIVVJXRND-UHFFFAOYSA-N 0.000 description 4
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- 239000012280 lithium aluminium hydride Substances 0.000 description 4
- DLEDOFVPSDKWEF-UHFFFAOYSA-N lithium butane Chemical compound [Li+].CCC[CH2-] DLEDOFVPSDKWEF-UHFFFAOYSA-N 0.000 description 4
- HQKMJHAJHXVSDF-UHFFFAOYSA-L magnesium stearate Chemical compound [Mg+2].CCCCCCCCCCCCCCCCCC([O-])=O.CCCCCCCCCCCCCCCCCC([O-])=O HQKMJHAJHXVSDF-UHFFFAOYSA-L 0.000 description 4
- 235000010755 mineral Nutrition 0.000 description 4
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- WUNCNRPCDJSLBX-UHFFFAOYSA-N 4-(2-phenylbut-1-enyl)-1-tritylimidazole Chemical compound C=1C=CC=CC=1C(CC)=CC(N=C1)=CN1C(C=1C=CC=CC=1)(C=1C=CC=CC=1)C1=CC=CC=C1 WUNCNRPCDJSLBX-UHFFFAOYSA-N 0.000 description 3
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- DNFKJSHGKYSOSP-UHFFFAOYSA-N 4-[(2-phenylmethoxyphenoxy)methyl]-1-tritylimidazole Chemical compound C=1N(C(C=2C=CC=CC=2)(C=2C=CC=CC=2)C=2C=CC=CC=2)C=NC=1COC1=CC=CC=C1OCC1=CC=CC=C1 DNFKJSHGKYSOSP-UHFFFAOYSA-N 0.000 description 3
- YTJOAWMAOMYSPA-UHFFFAOYSA-N 5-(1-methoxy-2-phenylethyl)-1h-imidazole Chemical compound C=1NC=NC=1C(OC)CC1=CC=CC=C1 YTJOAWMAOMYSPA-UHFFFAOYSA-N 0.000 description 3
- CVXWUKSPKVSQRP-UHFFFAOYSA-N 5-[(2,6-dimethylphenoxy)methyl]-1h-imidazole Chemical compound CC1=CC=CC(C)=C1OCC1=CNC=N1 CVXWUKSPKVSQRP-UHFFFAOYSA-N 0.000 description 3
- WRAZSLKGTVFTSN-UHFFFAOYSA-N 5-[2-(2,6-dimethylphenyl)ethyl]-1h-imidazole Chemical compound CC1=CC=CC(C)=C1CCC1=CN=CN1 WRAZSLKGTVFTSN-UHFFFAOYSA-N 0.000 description 3
- XTHFKEDIFFGKHM-UHFFFAOYSA-N Dimethoxyethane Chemical compound COCCOC XTHFKEDIFFGKHM-UHFFFAOYSA-N 0.000 description 3
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- MUBZPKHOEPUJKR-UHFFFAOYSA-N Oxalic acid Chemical compound OC(=O)C(O)=O MUBZPKHOEPUJKR-UHFFFAOYSA-N 0.000 description 3
- 239000012317 TBTU Substances 0.000 description 3
- RTAQQCXQSZGOHL-UHFFFAOYSA-N Titanium Chemical compound [Ti] RTAQQCXQSZGOHL-UHFFFAOYSA-N 0.000 description 3
- DTQVDTLACAAQTR-UHFFFAOYSA-N Trifluoroacetic acid Chemical compound OC(=O)C(F)(F)F DTQVDTLACAAQTR-UHFFFAOYSA-N 0.000 description 3
- CLZISMQKJZCZDN-UHFFFAOYSA-N [benzotriazol-1-yloxy(dimethylamino)methylidene]-dimethylazanium Chemical compound C1=CC=C2N(OC(N(C)C)=[N+](C)C)N=NC2=C1 CLZISMQKJZCZDN-UHFFFAOYSA-N 0.000 description 3
- 239000000654 additive Substances 0.000 description 3
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- 239000012298 atmosphere Substances 0.000 description 3
- 150000001728 carbonyl compounds Chemical class 0.000 description 3
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- UBJFKNSINUCEAL-UHFFFAOYSA-N lithium;2-methylpropane Chemical compound [Li+].C[C-](C)C UBJFKNSINUCEAL-UHFFFAOYSA-N 0.000 description 1
- WGOPGODQLGJZGL-UHFFFAOYSA-N lithium;butane Chemical compound [Li+].CC[CH-]C WGOPGODQLGJZGL-UHFFFAOYSA-N 0.000 description 1
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- TWRXJAOTZQYOKJ-UHFFFAOYSA-L magnesium chloride Substances [Mg+2].[Cl-].[Cl-] TWRXJAOTZQYOKJ-UHFFFAOYSA-L 0.000 description 1
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- 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 description 1
- WBYWAXJHAXSJNI-UHFFFAOYSA-N methyl p-hydroxycinnamate Natural products OC(=O)C=CC1=CC=CC=C1 WBYWAXJHAXSJNI-UHFFFAOYSA-N 0.000 description 1
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- UKODFQOELJFMII-UHFFFAOYSA-N pentamethyldiethylenetriamine Chemical compound CN(C)CCN(C)CCN(C)C UKODFQOELJFMII-UHFFFAOYSA-N 0.000 description 1
- 210000001428 peripheral nervous system Anatomy 0.000 description 1
- 238000011458 pharmacological treatment Methods 0.000 description 1
- 150000003008 phosphonic acid esters Chemical class 0.000 description 1
- IUBQJLUDMLPAGT-UHFFFAOYSA-N potassium bis(trimethylsilyl)amide Chemical compound C[Si](C)(C)N([K])[Si](C)(C)C IUBQJLUDMLPAGT-UHFFFAOYSA-N 0.000 description 1
- 239000002244 precipitate Substances 0.000 description 1
- 239000003755 preservative agent Substances 0.000 description 1
- ALSRTSXZMQADEF-UHFFFAOYSA-N propan-2-yl 2-iodylbenzoate Chemical compound CC(C)OC(=O)C1=CC=CC=C1I(=O)=O ALSRTSXZMQADEF-UHFFFAOYSA-N 0.000 description 1
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- KRIOVPPHQSLHCZ-UHFFFAOYSA-N propiophenone Chemical compound CCC(=O)C1=CC=CC=C1 KRIOVPPHQSLHCZ-UHFFFAOYSA-N 0.000 description 1
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- 238000000159 protein binding assay Methods 0.000 description 1
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- UMJSCPRVCHMLSP-UHFFFAOYSA-N pyridine Natural products COC1=CC=CN=C1 UMJSCPRVCHMLSP-UHFFFAOYSA-N 0.000 description 1
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- IUVKMZGDUIUOCP-BTNSXGMBSA-N quinbolone Chemical compound O([C@H]1CC[C@H]2[C@H]3[C@@H]([C@]4(C=CC(=O)C=C4CC3)C)CC[C@@]21C)C1=CCCC1 IUVKMZGDUIUOCP-BTNSXGMBSA-N 0.000 description 1
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- 229940076279 serotonin Drugs 0.000 description 1
- WRIKHQLVHPKCJU-UHFFFAOYSA-N sodium bis(trimethylsilyl)amide Chemical compound C[Si](C)(C)N([Na])[Si](C)(C)C WRIKHQLVHPKCJU-UHFFFAOYSA-N 0.000 description 1
- 229910052938 sodium sulfate Inorganic materials 0.000 description 1
- 235000011152 sodium sulphate Nutrition 0.000 description 1
- XMVONEAAOPAGAO-UHFFFAOYSA-N sodium tungstate Chemical compound [Na+].[Na+].[O-][W]([O-])(=O)=O XMVONEAAOPAGAO-UHFFFAOYSA-N 0.000 description 1
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Classifications
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- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D233/00—Heterocyclic compounds containing 1,3-diazole or hydrogenated 1,3-diazole rings, not condensed with other rings
- C07D233/54—Heterocyclic compounds containing 1,3-diazole or hydrogenated 1,3-diazole rings, not condensed with other rings having two double bonds between ring members or between ring members and non-ring members
- C07D233/64—Heterocyclic compounds containing 1,3-diazole or hydrogenated 1,3-diazole rings, not condensed with other rings having two double bonds between ring members or between ring members and non-ring members with substituted hydrocarbon radicals attached to ring carbon atoms, e.g. histidine
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K31/00—Medicinal preparations containing organic active ingredients
- A61K31/33—Heterocyclic compounds
- A61K31/395—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins
- A61K31/41—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having five-membered rings with two or more ring hetero atoms, at least one of which being nitrogen, e.g. tetrazole
- A61K31/415—1,2-Diazoles
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- A—HUMAN NECESSITIES
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- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
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- A61P25/06—Antimigraine agents
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- A61P25/18—Antipsychotics, i.e. neuroleptics; Drugs for mania or schizophrenia
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- A—HUMAN NECESSITIES
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- A61P25/00—Drugs for disorders of the nervous system
- A61P25/28—Drugs for disorders of the nervous system for treating neurodegenerative disorders of the central nervous system, e.g. nootropic agents, cognition enhancers, drugs for treating Alzheimer's disease or other forms of dementia
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- A61P25/30—Drugs for disorders of the nervous system for treating abuse or dependence
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- A61P3/00—Drugs for disorders of the metabolism
- A61P3/08—Drugs for disorders of the metabolism for glucose homeostasis
- A61P3/10—Drugs for disorders of the metabolism for glucose homeostasis for hyperglycaemia, e.g. antidiabetics
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Landscapes
- Health & Medical Sciences (AREA)
- Chemical & Material Sciences (AREA)
- Organic Chemistry (AREA)
- Engineering & Computer Science (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Pharmacology & Pharmacy (AREA)
- Veterinary Medicine (AREA)
- Public Health (AREA)
- General Health & Medical Sciences (AREA)
- Animal Behavior & Ethology (AREA)
- Medicinal Chemistry (AREA)
- Life Sciences & Earth Sciences (AREA)
- General Chemical & Material Sciences (AREA)
- Chemical Kinetics & Catalysis (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- Biomedical Technology (AREA)
- Neurosurgery (AREA)
- Neurology (AREA)
- Diabetes (AREA)
- Psychiatry (AREA)
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- Hematology (AREA)
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- Pain & Pain Management (AREA)
- Emergency Medicine (AREA)
- Addiction (AREA)
- Heart & Thoracic Surgery (AREA)
- Cardiology (AREA)
- Hospice & Palliative Care (AREA)
- Endocrinology (AREA)
- Child & Adolescent Psychology (AREA)
- Epidemiology (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Plural Heterocyclic Compounds (AREA)
Applications Claiming Priority (3)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| EP06126307.5 | 2006-12-18 | ||
| EP06126307 | 2006-12-18 | ||
| PCT/EP2007/063585 WO2008074679A2 (en) | 2006-12-18 | 2007-12-10 | 4-imidazolines as taar's ligands |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| CA2671838A1 true CA2671838A1 (en) | 2008-06-26 |
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Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| CA002671838A Abandoned CA2671838A1 (en) | 2006-12-18 | 2007-12-10 | 4-imidazolines as taar's ligands |
Country Status (18)
| Country | Link |
|---|---|
| US (3) | US20080146523A1 (zh) |
| EP (1) | EP2094668A2 (zh) |
| JP (1) | JP5175297B2 (zh) |
| KR (1) | KR101188992B1 (zh) |
| CN (1) | CN101578271B (zh) |
| AR (1) | AR064376A1 (zh) |
| AU (1) | AU2007336351A1 (zh) |
| BR (1) | BRPI0721291A2 (zh) |
| CA (1) | CA2671838A1 (zh) |
| CL (1) | CL2007003653A1 (zh) |
| IL (1) | IL198878A0 (zh) |
| MX (1) | MX2009006215A (zh) |
| NO (1) | NO20091936L (zh) |
| PE (1) | PE20081386A1 (zh) |
| RU (1) | RU2465269C2 (zh) |
| TW (1) | TWI345467B (zh) |
| WO (1) | WO2008074679A2 (zh) |
| ZA (1) | ZA200903841B (zh) |
Families Citing this family (8)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CA2676944C (en) | 2007-02-15 | 2016-01-19 | F. Hoffmann-La Roche Ag | 2-aminooxazolines as taar1 ligands |
| EP2242745A1 (de) * | 2008-02-07 | 2010-10-27 | Sanofi-Aventis | Neue phenyl-substituierte imidazolidine, verfahren zu deren herstellung, diese verbindungen enthaltende arzneimittel und deren verwendung |
| WO2012078817A1 (en) | 2010-12-08 | 2012-06-14 | Vanderbilt University | Bicyclic pyrazole compounds as allosteric modulators of mglur5 receptors |
| US8865725B2 (en) | 2011-03-15 | 2014-10-21 | Vanderbilt University | Substituted imidazopyrimidin-5(6H)-ones as allosteric modulators of MGLUR5 receptors |
| JP2014508172A (ja) * | 2011-03-15 | 2014-04-03 | ヴァンダービルト ユニバーシティー | Ｍｇｌｕｒ５受容体のアロステリック調節剤としての置換イミダゾピリミジン−５（６ｈ）−オン |
| EP2567959B1 (en) | 2011-09-12 | 2014-04-16 | Sanofi | 6-(4-hydroxy-phenyl)-3-styryl-1h-pyrazolo[3,4-b]pyridine-4-carboxylic acid amide derivatives as kinase inhibitors |
| CN103910658B (zh) * | 2013-12-23 | 2016-08-17 | 宁夏大学 | 一种硫醚氧化成砜的方法 |
| WO2015165085A1 (en) | 2014-04-30 | 2015-11-05 | F.Hoffmann-La Roche Ag | Morpholin-pyridine derivatives |
Family Cites Families (68)
| Publication number | Priority date | Publication date | Assignee | Title |
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| US2731471A (en) * | 1956-01-17 | Nxg hi | ||
| US2161938A (en) * | 1934-07-31 | 1939-06-13 | Soc Of Chemical Ind | Imidazolines |
| US2457047A (en) * | 1946-02-13 | 1948-12-21 | Monsanto Chemicals | 2-(2'-thenyl)-4, 5-dihydroimidazoles and process for making the same |
| GB725514A (en) | 1952-08-28 | 1955-03-02 | Abbott Lab | Improvements in or relating to 4(5)-aryloxymethylimidazoles and their preparation |
| US2778836A (en) * | 1954-04-02 | 1957-01-22 | Union Chimique Belge Sa | Substituted 2-methyl-delta2 imidazolines |
| US2744910A (en) * | 1955-06-27 | 1956-05-08 | Bristol Lab Inc | 2-(ortho-benzylbenzyl)-imidazoline and acid addition salts |
| US2744909A (en) * | 1955-06-27 | 1956-05-08 | Bristol Lab Inc | 2-(ortho-phenylbenzyl) imidazoline and acid addition salts |
| US2919274A (en) * | 1957-09-17 | 1959-12-29 | Sahyun Melville | Amidines |
| GB877306A (en) | 1958-04-21 | 1961-09-13 | Pfizer & Co C | Halogenated derivatives of tetrahydro-1-naphthyl cyclic amidines |
| DE1121054B (de) * | 1960-11-23 | 1962-01-04 | Merck Ag E | Verfahren zur Herstellung eines neuen Imidazolinderivates und dessen Saeureadditionssalzen |
| US3202660A (en) | 1961-10-09 | 1965-08-24 | Boehringer Sohn Ingelheim | Process for the preparation of 3-arylamino-1, 3-diazacycloalkenes |
| DE1150180B (de) * | 1962-04-12 | 1963-06-12 | Merck Ag E | Mittel zur Vorbehandlung der Haut fuer die Rasur |
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-
2007
- 2007-12-05 US US11/950,449 patent/US20080146523A1/en not_active Abandoned
- 2007-12-10 CN CN2007800469972A patent/CN101578271B/zh not_active Expired - Fee Related
- 2007-12-10 EP EP07857315A patent/EP2094668A2/en not_active Withdrawn
- 2007-12-10 MX MX2009006215A patent/MX2009006215A/es active IP Right Grant
- 2007-12-10 RU RU2009122665/04A patent/RU2465269C2/ru not_active IP Right Cessation
- 2007-12-10 CA CA002671838A patent/CA2671838A1/en not_active Abandoned
- 2007-12-10 BR BRPI0721291-7A patent/BRPI0721291A2/pt not_active IP Right Cessation
- 2007-12-10 JP JP2009541972A patent/JP5175297B2/ja not_active Expired - Fee Related
- 2007-12-10 KR KR1020097012493A patent/KR101188992B1/ko not_active IP Right Cessation
- 2007-12-10 AU AU2007336351A patent/AU2007336351A1/en not_active Abandoned
- 2007-12-10 WO PCT/EP2007/063585 patent/WO2008074679A2/en active Application Filing
- 2007-12-14 PE PE2007001804A patent/PE20081386A1/es not_active Application Discontinuation
- 2007-12-17 CL CL200703653A patent/CL2007003653A1/es unknown
- 2007-12-17 AR ARP070105650A patent/AR064376A1/es unknown
- 2007-12-17 TW TW096148251A patent/TWI345467B/zh not_active IP Right Cessation
-
2009
- 2009-05-19 NO NO20091936A patent/NO20091936L/no not_active Application Discontinuation
- 2009-05-21 IL IL198878A patent/IL198878A0/en unknown
- 2009-06-02 ZA ZA200903841A patent/ZA200903841B/xx unknown
-
2010
- 2010-04-23 US US12/765,898 patent/US20100204233A1/en not_active Abandoned
-
2011
- 2011-09-19 US US13/235,542 patent/US8399463B2/en not_active Expired - Fee Related
Also Published As
| Publication number | Publication date |
|---|---|
| AU2007336351A1 (en) | 2008-06-26 |
| CN101578271A (zh) | 2009-11-11 |
| US20120004230A1 (en) | 2012-01-05 |
| EP2094668A2 (en) | 2009-09-02 |
| NO20091936L (no) | 2009-07-14 |
| JP5175297B2 (ja) | 2013-04-03 |
| TW200833327A (en) | 2008-08-16 |
| KR20090081431A (ko) | 2009-07-28 |
| US8399463B2 (en) | 2013-03-19 |
| US20100204233A1 (en) | 2010-08-12 |
| US20080146523A1 (en) | 2008-06-19 |
| BRPI0721291A2 (pt) | 2014-03-25 |
| RU2465269C2 (ru) | 2012-10-27 |
| PE20081386A1 (es) | 2008-09-18 |
| MX2009006215A (es) | 2009-06-22 |
| WO2008074679A2 (en) | 2008-06-26 |
| TWI345467B (en) | 2011-07-21 |
| CL2007003653A1 (es) | 2008-07-11 |
| JP2010513373A (ja) | 2010-04-30 |
| KR101188992B1 (ko) | 2012-10-08 |
| ZA200903841B (en) | 2010-03-31 |
| AR064376A1 (es) | 2009-04-01 |
| WO2008074679A3 (en) | 2008-10-09 |
| IL198878A0 (en) | 2010-02-17 |
| CN101578271B (zh) | 2013-06-19 |
| RU2009122665A (ru) | 2011-01-27 |
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| EEER | Examination request | ||
| FZDE | Discontinued |
Effective date: 20150604 |